AZD4721 / Aristea, Pfizer - LARVOL DELTA

A Systematic Review of Pharmacological Interventions for Hidradenitis Suppurativa: A Focus on Clinical Response, Quality of Life, and Safety (ISPOR-EU 2024) - "Adalimumab, anakinra, apremilast, avacopan, bimekizumab, doxycycline, guselkumab, IFX-1, MABp1, PF-06650833, PF-06700841, PF-06826647, povorcitinib, risankizumab, RIST4721, secukinumab, upadacitinib all reported notable clinical benefits, with Hidradenitis Suppurativa Clinical Response (HiSCR) ranged from 10% (anakinra at week 24) to 88% (povorcitinib-90 mg at week 8)...In contrast, no SAEs were detected in spesolimab or anakinra, while bimekizumab had similar safety profiles to adalimumab. The results of this review demonstrate the possibility of highly personalized treatment approaches for HS management, including adalimumab and povorcitinib. The optimization of HS care requires further research on long-term outcomes."

Clinical • HEOR • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Pain

A systematic review of recent randomized controlled trials for palmoplantar pustulosis. (PubMed, J Dermatolog Treat) - " Phototherapy showed success: excimer laser demonstrated high efficacy for severe disease [PPP Area and Severity Index (PPPASI)-75 of 95.0%], while psoralen plus ultraviolet A therapy with retinoids or fumaric acid esters worked well in milder disease (PPPASI-90 of 90.0 and 81.8%, respectively). Evidence supports the efficacy and safety of guselkumab, brodalumab, and apremilast over a range of disease severity (PPPASI-50 ranged from 57.4 to 78.3% at week 16). Agents including anakinra, secukinumab, spesolimab, and RIST4721 (primary outcomes not achieved) may not be first-line treatments. By targeting multiple inflammatory pathways in PPP, JAK inhibitors may be more effective than biologics in treating PPP; however, more research is needed to confirm their safety and appropriate use. Multiple new treatments exist for PPP with promising results, however longer-term studies with standardized outcome reporting are needed to determine optimal treatment strategies and their..."

Journal • Review • Dermatology • Immunology • Psoriasis • Pustular Psoriasis

Pfizer Cuts Mid-Stage Candidates Amid Declining Revenues (BioSpace) - "Fresh off its $43 billion acquisition of Seagen, Pfizer is making deep cuts to its Phase II pipeline in cardiology and inflammatory diseases, the company revealed Tuesday during its first-quarter financial report. On Pfizer’s chopping block is temanogrel, an inverse agonist of the serotonin 2A receptor being trialed for microvascular obstruction and Raynaud’s phenomenon related to systemic sclerosis. Pfizer is also dumping its cardio candidate APD418, an antagonist of the beta-3 adrenergic receptor in Phase II studies for acute heart failure...Pfizer’s pipeline clean-out also included the biologic blocker of the TNFSF15 protein for ulcerative colitis and the CXCR2 antagonist RIST4721, which was in Phase II studies for hidradenitis suppurativa and palmoplantar pustulosis."

Pipeline update • Cardiovascular • Heart Failure • Hidradenitis Suppurativa • Immunology • Myocardial Ischemia

A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2a | N=25 | Terminated | Sponsor: Aristea Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Feb 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2023 ➔ Feb 2023; Due to safety findings in ongoing Phase 2 trials.

Trial completion date • Trial primary completion date • Trial termination • Dermatology • Hidradenitis Suppurativa

A Phase 2b Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP) (clinicaltrials.gov) - P2b | N=79 | Terminated | Sponsor: Aristea Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Mar 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2023 ➔ Feb 2023; Due to safety findings in ongoing Phase 2 trials.

Trial completion date • Trial primary completion date • Trial termination • Immunology • Psoriasis

CXCR2 Antagonist RIST4721 Acts as a Potent Chemotaxis Inhibitor of Mature Neutrophils Derived from Ex Vivo-Cultured Mouse Bone Marrow. (PubMed, Biomedicines) - "Importantly, RIST4721-treated neutrophils exhibit robust phagocytosis and reactive oxygen species production, confirming drug specificity to chemotaxis inhibition. Together our data indicate that RIST4721 acts to inhibit inflammation mediated and potentiated by neutrophils and therefore promises to facilitate treatment of a host of inflammatory conditions."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Oncology • CXCR2

A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2a | N=25 | Active, not recruiting | Sponsor: Aristea Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Hidradenitis Suppurativa

Aristea Therapeutics Announces Discontinuation of RIST4721 Development Program and Decision to Dissolve the Company (PRNewswire) - "Aristea Therapeutics...today announced that, due to safety findings in the ongoing Phase 2 clinical trials, it has discontinued the RIST4721 development program in order to protect patient safety."

Discontinued • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

A Study to Evaluate RIST4721 in Familial Mediterranean Fever (FMF) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Aristea Therapeutics, Inc. | N=20 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders

A Phase 2b Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP) (clinicaltrials.gov) - P2b | N=79 | Active, not recruiting | Sponsor: Aristea Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=156 ➔ 79

Enrollment change • Enrollment closed • Immunology • Psoriasis

A Study to Evaluate RIST4721 in Familial Mediterranean Fever (FMF) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Aristea Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Dec 2024 | Trial primary completion date: May 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • Genetic Disorders

A Phase 2b Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP) (clinicaltrials.gov) - P2b; N=156; Recruiting; Sponsor: Aristea Therapeutics, Inc.

Clinical • New P2b trial • Immunology • Psoriasis

A Phase 2b Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP) (clinicaltrials.gov) - P2b | N=156 | Recruiting | Sponsor: Aristea Therapeutics, Inc. | Trial completion date: May 2023 ➔ Dec 2024

Trial completion date • Immunology • Psoriasis

A Study to Evaluate RIST4721 in Familial Mediterranean Fever (FMF) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Aristea Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2a | N=33 | Recruiting | Sponsor: Aristea Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Hidradenitis Suppurativa

A Study to Evaluate RIST4721 in Familial Mediterranean Fever (FMF) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Aristea Therapeutics, Inc.

New P2 trial • Genetic Disorders

RIST4721 in Subjects with Palmoplantar Pustulosis (clinicaltrialsregister.eu) - P2 | N=156 | Ongoing | Sponsor: Aristea Therapeutics Inc.

New P2 trial • Immunology • Psoriasis • Rheumatology

A Study to Evaluate RIST4721 in Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2a | N=33 | Not yet recruiting | Sponsor: Aristea Therapeutics, Inc.

New P2a trial • Dermatology • Hidradenitis Suppurativa

A Study of the ADME of [14C]RIST4721 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Completed; Sponsor: Aristea Therapeutics, Inc.; Recruiting ➔ Completed

Clinical • Trial completion

Possible extraction of drugs from lung tissue during broncho-alveolar lavage suggest uncertainty in the procedure's utility for quantitative assessment of airway drug exposure. (PubMed, J Pharm Sci) - "As representatives of permeable small molecule drugs with high, medium and low tissue distribution properties, propranolol, diazepam, indomethacin and AZD4721 were infused intravenously to steady state to ensure equal unbound drug concentrations throughout the body. In addition, the results show that the unbound concentrations in ELF compared to plasma differs dependent on molecule class and tissue distribution properties. Overall data suggests that lavaging can remove drug from lung tissue in addition to ELF and highlights significant uncertainty in the robustness of the procedure for determining ELF drug concentrations."

Journal

A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis. (PubMed, Dermatol Ther (Heidelb)) - P2a | "Preliminary data suggest RIST4721 is well tolerated and may be a potential therapy for patients with PPP."

Clinical • Journal • P2a data • Immunology • Psoriasis • CXCR2

A Study of the ADME of [14C]RIST4721 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Recruiting; Sponsor: Aristea Therapeutics, Inc.

Clinical • New P1 trial

Arena Pharmaceuticals and Aristea Therapeutics Establish Collaboration for Development of RIST4721 for Treatment of Serious Immune-Mediated Inflammatory Diseases (Businesswire) - "Arena Pharmaceuticals, Inc...and Aristea Therapeutics, Inc. today announced a strategic collaboration to advance the clinical development of RIST4721, an oral CXCR2 antagonist being developed by Aristea for the treatment of palmoplantar pustulosis (PPP) and other neutrophil-mediated diseases...The agreement also provides a framework during the option period for the companies to jointly explore the development of additional neutrophil-mediated diseases, including...inflammatory bowel disease (IBD), potentially generating multiple data readouts during the option period."

Licensing / partnership • Immunology • Inflammatory Bowel Disease

[VIRTUAL] Results from RIST4721-201, A Randomized, Double-Blind, Placebo controlled exploratory Phase 2a study in subjects with Palmoplantar Pustulosis (EADV 2020) - No abstract available

Clinical • Late-breaking abstract • P2a data • Immunology • Psoriasis

A Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP) (clinicaltrials.gov) - P2a; N=35; Completed; Sponsor: Aristea Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Psoriasis